Involvement of CD28/CTLA4-B7 Costimulatory Pathway in the Development of Lymphadenopathy and Splenomegaly in MRL/lpr Mice

Mitsuyoshi Takiguchi, Masaaki Murakami, Izumi Nakagawa, Mohammod Misanur Rashid, Noriko Tosa, Shunsuke Chikuma, Akira Hashimoto, Toshimitsu Uede

Research output: Contribution to journalArticle

3 Citations (Scopus)


MRL/lpr mouse is an established animal model which develops autoimmune diseases including glomerulonephritis, sialoadenitis, hepatitis and inflammatory lung disease. Additionally, it has been reported that lpr strains uniquely accumulate CD3+CD4-CD8-B220+ (double negative, DN) T cells in lymphoid organs leading to lymphadenopathy and splenomegaly. To investigate the role of CD28/CTLA4-B7 pathway in the development of lymphadenopathy and splenomegaly, MRL/lpr mice were treated with soluble form of CTLA4 molecules, CTLA4IgG, which efficiently blocks this pathway. It was demonstrated that (i) the development of DN T cells was independent of the CD28/CTLA4-B7 pathway, (ii) the CD28/CTLA4-B7 pathway was required for the development of lymphadenopathy and splenomegaly, (iii) the CD28/CTLA4-B7 pathway was important for the accumulation of various cell populations in the lymph node and spleen, (iv) composition of the accumulating cell populations was not altered by CTLA4IgG treatment, and (v) activation of conventional T cells and IL-4 production from conventional T cells were the CD28/CTLA4-B7 pathway dependent. Thus, we concluded that the CD28/CTLA4-B7 pathway was required for the development of full-blown lymphadenopathy and splenomegaly in MRL/lpr mice.

Original languageEnglish
Pages (from-to)29-36
Number of pages8
JournalJournal of Veterinary Medical Science
Issue number1
Publication statusPublished - 2000 Jan



  • CTLA4IgG
  • Costimulatory signal
  • IL-4
  • Lymphadenopathy
  • MRL/lpr

ASJC Scopus subject areas

  • veterinary(all)

Cite this